Metabolism of lipid peroxidation product, 4-hydroxynonenal (HNE) in rat erythrocytes: Role of aldose reductase

Sanjay Srivastava, Bharat L. Dixit, Jian Cai, Silky Sharma, Harrell E. Hurst, Aruni Bhatnagar, Satish K. Srivastava

Research output: Contribution to journalArticlepeer-review

110 Scopus citations


Lipid peroxidation represents a significant source of erythrocyte dysfunction and aging. Because the toxicity of lipid peroxidation appears to be in part due to aldehydic end products, we examined, in rat erythrocytes, the metabolism of 4-hydroxy-trans-2-nonenal (HNE), one of the most abundant and toxic lipid-derived aldehydes. Packed erythrocytes, 0.1 ml, completely metabolized 20 nmoles of HNE in 20 min. The glutathione conjugate of HNE and 4-hydroxynonanoic acid (HNA) represented 70 and 25% of the total metabolism, respectively. Approximately 70% of the metabolites were extruded to the medium. Upon electrospray ionization mass spectrometry, the glutathione conjugate resolved into two distinct species corresponding to glutathionyl HNE (GS-HNE) and glutathionyl 1,4-dihydroxynonene (GS-DHN). The concentration of GS-DHN formed was twice that of GS-HNE. Inhibition of aldose reductase by sorbinil and tolrestat led to a selective decrease in the formation of GS-DHN, although the extent of HNE glutathiolation was unaffected. Inhibitors of aldehyde or alcohol dehydrogenase, i.e., cyanamide and 4-methyl pyrazole, had no effect on the formation of HNA and GS-DHN, indicating that these enzymes are not significant participants in the erythrocyte HNE metabolism. Thus, oxidation to HNA, conjugation with glutathione, and further reduction of the conjugate by aldose reductase appear to be the major pathways of HNE metabolism in erythrocytes. These pathways may be critical determinants of erythrocyte toxicity due to lipid peroxidation-derived aldehydes. Copyright (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)642-651
Number of pages10
JournalFree Radical Biology and Medicine
Issue number7
StatePublished - 2000
Externally publishedYes


  • 4-hydroxy-trans-2-nonenal
  • Aldose reductase
  • Erythrocytes
  • Free radicals
  • Glutathione
  • Lipid peroxidation

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


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